Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular parasite which is generally transmitted from animals to humans. Domestic livestock serve as a reservoir for Q fever in most parts of the world, and usually presents as an inapparent infection; in sheep, however, it may lead to late-term abortion. In domestic animals (sheep, goats, cattle), the disease is shed and transmitted either by aerosol or through an intermediate vector (tick). Further, apparently healthy animals may contain enormous numbers of parasites in placental tissues. (Luoto & Huebner, Public Health Rep. 65:541-544, 1950).
Although Q fever may be transmitted to humans by ticks, it is usually contracted by inhalation of contaminated dusts and aerosols; contagion between humans is rare. Coxiella burnetii is known to infect many species of animals and birds (Babudieri, B., Adv. Vet. Sci. 5:81-154, 1959). Q fever is most common among slaughterhouse employees and farm workers who handle animals (domestic cattle, sheep and goats) or animal products (e.g., wool, hides) (Ormsbee, R. A., Ann. Rev. Microbiol. 23:275-292 (1962); Baca & Paretsky, Microbiol. Rev. 47:127-149, 1983).
The acute form of Q fever is rarely fatal to humans. The death rate has been estimated at less than 1% among Caucasians, and somewhat higher among indigenous people of equatorial Africa (Ormsbee, R. A., Viral and Rickettsial Infections of Man; 4th Ed., ed. F. L. Horsfall Jr. and I. Tamm, pp. 1144-1160, 1965, J. B. Lippincott Co., Penn.). The incubation period ranges from 1 to 3 weeks, and the disease normally presents as an acute febrile illness. Recovery generally occurs within 1 to 4 weeks, depending on the course of treatment. Occasionally, C. burnetii infection is manifested in other ways, including inapparent persistent infection, which can lead to endocarditis or other symptoms in man. The development of chronic endocarditis in humans has previously been thought to arise when a C. burnetii infection is superimposed on a pre-existing disease or deformity of the patient, rather than to a specific property of the pathogen (Peacock et al., Infect. & Immun. 41:1089-1098, 1983; Turck et al., J. of Medicine 178:193-217, 1976; Tobin et al., Amer. J. of Med. 72: 396-399, 1982; Robson et al., British Med. J. 2:980-983, 1959). Comparative analyses of infected sera and of the biological properties of microorganisms isolated from various sequelae of Q fever (acute infection, chronic endocarditis, abortion, etc.) have not indicated that specific C. burnetii variants produce a particular manifestation. Comparative analyses have, however, demonstrated antigenic variation in C. burnetii (Stoker, M. G. P. and P. Fiset, Can. J. Microbiol. 2:310-321, 1956). This antigenic phase variation is characterized primarily by the reactivity of different isolates with hyperimmune sera against phase I or phase II Nine Mile strain of C. burnetii. However, this phenotypic variation cannot be used to predict sequelae of C. burnetii infection.
Differentiation of Q fever from influenza, primary atypical pneumonia, bacterial pneumonia, or a number of other types of pneumonia and flu-like symptoms caused by a variety of etiological agents is a slow and difficult process. It is also difficult to differentiate C. burnetti-induced hepatitis from infectious or idiopathic hepatitis. Differentiation procedures presently used require isolation of C. burnetii from tissues or blood, and subsequent culture in embryonated eggs or in guinea pigs. An alternative method for differentiation requires demonstration of a significant rise in specific anti-C. burnetii antibody titer in successive serum samples. Isolation of C. burnetii is highly hazardous, and is inadvisable in the absence of adequate (P-3) isolation facilities. Even then, safety procedures must be rigidly followed to avoid contamination. In addition, confirmation of findings usually takes 2 to 3 weeks. Serological methods, while simpler and safer than culturing, also require considerable time (usually 3 weeks) to confirm the diagnosis, and are therefore of little use to a practicing physician, who usually prefers to start treatment within 24 hours. In addition to being costly and time-consuming, both techniques require highly specialized facilities, equipment, and reagents that are generally available only in special laboratories. Furthermore, serological diagnosis of chronic Coxiella burnetii infections would be difficult since the appropriate (pre-immune) serum sample necessary for a definitive diagnosis would not be available.
Due to these difficulties in diagnosis, it is hard to accurately estimate the prevalence of C. burnetii infection throughout the world. Furthermore, there has been no way to predict from the initial symptoms the result of the infection, i.e., whether it will result in a persistent infection, including hepatitis and/or chronic endocarditis, or an acute attack of Q fever.
There exists a need in the art, then, for a rapid, sensitive, and simple method for the detection of C. burnetii in biological samples. In addition, a method for distinguishing C. burnetii strains capable of causing chronic infection from those associated only with acute infection would be useful for determining optimal patient treatment. The present invention fulfills these needs and further provides other related advantages.